Purkinje cell degeneration 8 Jackson
Son Yong Karst, Patricia F Ward-Bailey, Richard Sample, Kenneth R Johnson, Leah Rae Donahue and Muriel T Davisson
Source of Support:This research was supported by grants RR01183 to the Mouse Mutant Resource (M.T. Davisson, PI) and Cancer Core Grant CA34196.
Mutation (allele) symbol: Agtpbp1pcd-8J
Mutation (allele) name: Purkinje cell degeneration 8 Jackson
Gene symbol: Agtpbp1
Strain of origin: BALB/cJ
Current strain name: BALB/cJ-Agtpbp1pcd-8J/J
Stock #:008292 (View JAX®Mice Data Sheet for additional information including Price and Supply Information)
Phenotype categories: Neurological
Origin and Description
The neurological recessive Agtpbp1pcd-8J mutation arose spontaneously and was discovered by Teresa Torrey in a production colony of BALB/cJ mice at the Jackson Laboratory. Like the original Purkinje cell degeneration (pcd) mice, Agtpbp1pcd-8J mice are recognized by a moderate ataxia at 3-4 weeks of age. Homozygous mutant mice are smaller than litter mates, present the severe deficiency of Purkinje cells characteristic of other Agtpbp1 alleles and live through adulthood. Homozygous females are fertile but are very poor breeders. Males do not breed.
Genetic Analysis
Using our standard mapping protocols, a mutant mouse affected with the Agtpbp1pcd-8J mutation was mated to a CAST/EiJ mouse. No affected F1 mice were observed in the progeny produced by this mating. The F1 mice were then intercrossed and generated 41 affected F2 mice of which 23 were used for linkage analysis. The Agtpbp1pcd-8J mutation maps to Chromosome 13, proximal to D13Mit143 (NCBI 36 position 73.7Mb), and is non-recombinant with D13Mit157 (NCBI 36 position 60.0 mb) and D13Mit311 (NCBI 36 position 63.6 mb). Based on the chromosomal position from our initial mapping data and the phenotypic similarities with the original pcd mutants, a direct test for allelism was set up by mating 2 female mice heterozygous for this new mutation to a heterozygous male Agtpbp1pcd-3J mouse. This mating produced 13 pups of which 2 were affected with the mutant phenotype, proving allelism.
Pathology
A routine pathological screen of one female homozygous Agtpbp1pcd-8J mouse showed loss of Purkinje cells and had retinal degeneration at 7 weeks of age. One male homozygous mouse showed no Purkinje cells,but had retinal degeneration and abnormal sperm at 19 weeks of age.
Auditory brain stem response (ABR) testing of one homozygous mouse at 6 weeks of age revealed no hearing loss.
Electroretinogram testing (ERG) of the eyes of one homozygous male showed low rod and cone at 6 weeks of age. One female mouse homozygous for the Agtpbp1pcd-8J was also examined at 4 months of age and showed thin retinal vessels.
Acknowledgements
We thank Teresa Torrey for discovery of the mutant, Rod Bronson and Coleen Marden for pathological screening, Chantal Longo-Guess for hearing assessment, Norm Hawes and Ron Hurd for the eye examinations.
